Price Institute of Surgical Research and the Section of Colorectal Surgery, Hiram C. Polk Jr MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Ann Surg. 2012 Sep;256(3):544-51. doi: 10.1097/SLA.0b013e318265bd6f.
The main objective of this study was to investigate the potential use of circulating microRNAs (miRNAs) as biomarkers of sporadic colorectal cancer (CRC).
CRC, a leading cause of death, is curable if detected early. There is an unmet need for an accurate, noninvasive biomarker of CRC. MiRNAs are non-protein-coding RNAs regulating gene expression that play a role in CRC development.
Levels of 380 miRNAs were determined using microfluidic array technology (Applied Biosystems) in a "training" set of 30 CRC patients from whom cancer and adjacent normal tissue were collected. The 4 most dysregulated miRNAs (P < 0.05, false discovery rate (FDR): 10%) were then validated in a second blinded "test" set of 16 CRC patients from whom cancer and normal adjacent tissue had been collected. Validated tissue miRNAs were then evaluated in a plasma "test" set consisting of 30 CRC patients and 30 individuals without CRC. The most dysregulated tissue miRNAs were then validated in an independent new plasma test set consisting of 20 CRC patients with 20 age-, -, and race-matched subjects without CRC.
Nineteen of 380 miRNAs were dysregulated in CRC tissue in the tissue "training" set (P < 0.05, FDR: 10%). The 2 most upregulated (miR-31; miR-135b) and most downregulated (miR-1; miR-133a) miRNAs identified CRC in our "test" set with 100% sensitivity and 80% specificity. MiR-31 was more upregulated in stages III and IV compared with stages I and II (P < 0.05). In the "plasma" group, miR-21 differentiated CRC patients from controls with 90% specificity and sensitivity.
Plasma miRNAs provide reliable and noninvasive markers for CRC. Plasma miR-21 warrants study in larger cohorts. It seems uniquely promising as a plasma biomarker for CRC.
本研究的主要目的是探讨循环 microRNAs（miRNAs）作为散发性结直肠癌（CRC）生物标志物的潜在用途。
CRC 是导致死亡的主要原因，如果早期发现，是可以治愈的。目前迫切需要一种准确、非侵入性的 CRC 生物标志物。miRNAs 是一种非蛋白编码 RNA，可调节基因表达，在 CRC 发生发展中发挥作用。
使用微流控芯片技术（Applied Biosystems）在 30 例 CRC 患者的“训练”组中测定 380 个 miRNA 的水平，从这些患者中采集了癌症和相邻正常组织。然后，对 16 例 CRC 患者的第二个盲“测试”组中的 4 个最失调的 miRNA（P <0.05，错误发现率（FDR）：10%）进行验证，从这些患者中采集了癌症和正常相邻组织。验证的组织 miRNA 然后在由 30 例 CRC 患者和 30 例无 CRC 的个体组成的血浆“测试”组中进行评估。然后在由 20 例 CRC 患者和 20 例年龄、性别和种族匹配的无 CRC 对照组成的独立新血浆测试组中验证最失调的组织 miRNA。
在组织“训练”组中，380 个 miRNA 中有 19 个在 CRC 组织中失调（P <0.05，FDR：10%）。我们的“测试”组中上调最明显的（miR-31；miR-135b）和下调最明显的（miR-1；miR-133a）miRNA 以 100%的灵敏度和 80%的特异性识别 CRC。miR-31 在 III 期和 IV 期比 I 期和 II 期上调更明显（P <0.05）。在“血浆”组中，miR-21 以 90%的特异性和灵敏度区分 CRC 患者和对照组。
血浆 miRNA 为 CRC 提供了可靠、非侵入性的标志物。血浆 miR-21 值得在更大的队列中进行研究。它似乎是一种很有前途的 CRC 血浆生物标志物。
